Limits...
Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor.

Chen Y, Zhang W, Huang Y, Gao F, Fang X - Int J Nanomedicine (2015)

Bottom Line: Importantly, in vitro antiangiogenesis results demonstrated that c(RGDyK)-FP-DP had a significant inhibition effect on the tubular formation of human umbilical vein endothelial cells and promoted cellular apoptotic activity in MDR KBv cells.In addition, the growth inhibition efficacy of KBv tumor spheroids after crossing the blood-tumor barrier was obviously increased by c(RGDyK)-FP-DP compared to other control groups.Results suggested that c(RGDyK)-decorated Pluronic polymeric micelles can take pharmacological action on both human umbilical vein endothelial cells and KBv MDR cancer cells, resulting in a dual-functional anticancer effect similar to that observed in our in vitro cellular studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Fudan University, Shanghai, People's Republic of China ; Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.

ABSTRACT
Dual-functional drug delivery system was developed by decorating c(RGDyK) (cyclic RGD [arginine-glycine-aspartic acid] peptide) with Pluronic polymeric micelles (c[RGDyK]-FP-DP) to overcome the drawbacks of low transport of chemotherapeutics across the blood-tumor barrier and poor multidrug-resistant (MDR) tumor therapy. c(RGDyK) that can bind to the integrin protein richly expressed at the site of tumor vascular endothelial cells and tumor cells with high affinity and specificity was conjugated to the N-hydroxysuccinimide-activated PEO terminus of the Pluronic F127 block copolymer. In this study, decreased tumor angiogenic and increased apoptotic activity in MDR cancer cells were observed after the treatment with c(RGDyK)-FP-DP. c(RGDyK)-FP-DP was fully characterized in terms of morphology, particle size, zeta potential, and drug release. Importantly, in vitro antiangiogenesis results demonstrated that c(RGDyK)-FP-DP had a significant inhibition effect on the tubular formation of human umbilical vein endothelial cells and promoted cellular apoptotic activity in MDR KBv cells. In addition, the growth inhibition efficacy of KBv tumor spheroids after crossing the blood-tumor barrier was obviously increased by c(RGDyK)-FP-DP compared to other control groups. Results suggested that c(RGDyK)-decorated Pluronic polymeric micelles can take pharmacological action on both human umbilical vein endothelial cells and KBv MDR cancer cells, resulting in a dual-functional anticancer effect similar to that observed in our in vitro cellular studies.

No MeSH data available.


Related in: MedlinePlus

The characterization of PF-DP and c(RGDyK)-FP-DP micelles.Notes: (A) Transmission electron microscopy and (B) atomic force microscopy images of PF-DP and c(RGDyK)-FP-DP; (C) In vitro release of DOX and PTX from drug-loaded Pluronic micelles in phosphate buffered saline (pH 5.0 or 7.4) media with 0.2% Tween-80.Abbreviations: DOX, doxorubicin; PTX, paclitaxel; PF-DP, Pluronic micelles loaded with DOX and PTX; c(RGDyK)-FP-DP, c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX; c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4525800&req=5

f3-ijn-10-4863: The characterization of PF-DP and c(RGDyK)-FP-DP micelles.Notes: (A) Transmission electron microscopy and (B) atomic force microscopy images of PF-DP and c(RGDyK)-FP-DP; (C) In vitro release of DOX and PTX from drug-loaded Pluronic micelles in phosphate buffered saline (pH 5.0 or 7.4) media with 0.2% Tween-80.Abbreviations: DOX, doxorubicin; PTX, paclitaxel; PF-DP, Pluronic micelles loaded with DOX and PTX; c(RGDyK)-FP-DP, c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX; c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid.

Mentions: The mean diameter of both c(RGDyK)-FP-DP and PF-DP was found to be approximately 23 nm, with an acceptably good polydispersity index (PDI <0.2). Such micelles may accumulate in the tumor due to the enhanced permeability and retention effect.36 The particle size observed by TEM and AFM images were in good correspondence with that measured by the laser scattering technique (Figure 3A and B). The surface charge values were close to neutral (within ±5 mV). It was also found that there is no significant difference in drug-loading coefficient between c(RGDyK)-FP-DP and PF-DP (Table 1).


Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor.

Chen Y, Zhang W, Huang Y, Gao F, Fang X - Int J Nanomedicine (2015)

The characterization of PF-DP and c(RGDyK)-FP-DP micelles.Notes: (A) Transmission electron microscopy and (B) atomic force microscopy images of PF-DP and c(RGDyK)-FP-DP; (C) In vitro release of DOX and PTX from drug-loaded Pluronic micelles in phosphate buffered saline (pH 5.0 or 7.4) media with 0.2% Tween-80.Abbreviations: DOX, doxorubicin; PTX, paclitaxel; PF-DP, Pluronic micelles loaded with DOX and PTX; c(RGDyK)-FP-DP, c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX; c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525800&req=5

f3-ijn-10-4863: The characterization of PF-DP and c(RGDyK)-FP-DP micelles.Notes: (A) Transmission electron microscopy and (B) atomic force microscopy images of PF-DP and c(RGDyK)-FP-DP; (C) In vitro release of DOX and PTX from drug-loaded Pluronic micelles in phosphate buffered saline (pH 5.0 or 7.4) media with 0.2% Tween-80.Abbreviations: DOX, doxorubicin; PTX, paclitaxel; PF-DP, Pluronic micelles loaded with DOX and PTX; c(RGDyK)-FP-DP, c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX; c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid.
Mentions: The mean diameter of both c(RGDyK)-FP-DP and PF-DP was found to be approximately 23 nm, with an acceptably good polydispersity index (PDI <0.2). Such micelles may accumulate in the tumor due to the enhanced permeability and retention effect.36 The particle size observed by TEM and AFM images were in good correspondence with that measured by the laser scattering technique (Figure 3A and B). The surface charge values were close to neutral (within ±5 mV). It was also found that there is no significant difference in drug-loading coefficient between c(RGDyK)-FP-DP and PF-DP (Table 1).

Bottom Line: Importantly, in vitro antiangiogenesis results demonstrated that c(RGDyK)-FP-DP had a significant inhibition effect on the tubular formation of human umbilical vein endothelial cells and promoted cellular apoptotic activity in MDR KBv cells.In addition, the growth inhibition efficacy of KBv tumor spheroids after crossing the blood-tumor barrier was obviously increased by c(RGDyK)-FP-DP compared to other control groups.Results suggested that c(RGDyK)-decorated Pluronic polymeric micelles can take pharmacological action on both human umbilical vein endothelial cells and KBv MDR cancer cells, resulting in a dual-functional anticancer effect similar to that observed in our in vitro cellular studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Fudan University, Shanghai, People's Republic of China ; Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.

ABSTRACT
Dual-functional drug delivery system was developed by decorating c(RGDyK) (cyclic RGD [arginine-glycine-aspartic acid] peptide) with Pluronic polymeric micelles (c[RGDyK]-FP-DP) to overcome the drawbacks of low transport of chemotherapeutics across the blood-tumor barrier and poor multidrug-resistant (MDR) tumor therapy. c(RGDyK) that can bind to the integrin protein richly expressed at the site of tumor vascular endothelial cells and tumor cells with high affinity and specificity was conjugated to the N-hydroxysuccinimide-activated PEO terminus of the Pluronic F127 block copolymer. In this study, decreased tumor angiogenic and increased apoptotic activity in MDR cancer cells were observed after the treatment with c(RGDyK)-FP-DP. c(RGDyK)-FP-DP was fully characterized in terms of morphology, particle size, zeta potential, and drug release. Importantly, in vitro antiangiogenesis results demonstrated that c(RGDyK)-FP-DP had a significant inhibition effect on the tubular formation of human umbilical vein endothelial cells and promoted cellular apoptotic activity in MDR KBv cells. In addition, the growth inhibition efficacy of KBv tumor spheroids after crossing the blood-tumor barrier was obviously increased by c(RGDyK)-FP-DP compared to other control groups. Results suggested that c(RGDyK)-decorated Pluronic polymeric micelles can take pharmacological action on both human umbilical vein endothelial cells and KBv MDR cancer cells, resulting in a dual-functional anticancer effect similar to that observed in our in vitro cellular studies.

No MeSH data available.


Related in: MedlinePlus